The goal of this project is to identify genetic contributors to respiratory control and hypoxia tolerance. The hypoxic ventilatory response (HVR) is first line of defense when oxygen availability is reduced. The ability to sense hypoxia and increase ventilation is important for patients with respiratory diseases (e. g. sleep apnea, COPD), as well as in healthy individuals during ascent to high altitude. This project aims to (1) test the hypothesis that HVR variation is greater in ancestral highland populations compared to lowland populations, (2) test the hypothesis that an individual's HVR is explained by genetic factors related to hypoxia tolerance, and (3) to determine the role that gene expression plays in the acute response to hypoxia. Since the HVR is a key element in preventing respiratory disturbance in hypoxia, the results from this study will determine if disease progression can be predicted based on patient ancestral background. Therefore, this study will contribute to the development of individualized care and predictive strategies for pulmonary disease patients. Furthermore, this study will link genotypes to phenotypes by determining if the HVR is a function of patient genotype. These aims will be met by measuring the HVR and analyzing the expression of hypoxia-related candidate genes (e.g. EPAS-1, EGLN, HMOX2) in populations of highland and lowland ancestry. Native highlanders (Tibetans) demonstrate increased HVR variability as well as positive selection on these candidate genes compared to native lowland populations and therefore provide a valuable means for examining the relationship between genotype and the phenotypic hypoxia response. This research project is part of a postdoctoral training program in which the fellow will develop the skills necessary to launch a career as an independent biomedical scientist who will transform our understanding of lung disease and respiratory biology. The fellow will be supported by a network of pulmonary physiologist at UCSD and will focus on transforming basic science discoveries in to clinical practices.